| Project/Area Number |
14370449
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
OOHIRA Atsuhiko Aichi Human Service Center, Institute for Developmental Research, Department of Perinatology, Department Head, 周生期学部, 部長 (20101074)
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| Co-Investigator(Kenkyū-buntansha) |
TOKITA Yoshihito Aichi Human Service Center, Institute for Developmental Research, Department of Perinatology, Researcher, 周生期学部, 研究員 (50291175)
松井 ふみ子 愛知県心身障害者コロニー発達障害研究所, 周生期学部, 助手
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | neuroglycan C / chondroitin sulfate / proteoglycan / cell proliferation / neurite elongation / neural stem cell / kinase / bran injury / ADAM / FGF-2 / NGC / 情報伝達 / 上皮増殖因子(EGF) / ADAMTS-4 / 神経細胞 / アストログリア細胞 / 脳 / 脳損傷 / 虚血 / 低酸素 / 神経前駆細胞 / 新生児 |
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| Research Abstract |
The purpose of this project is identification of biologically active domains of neuroglycan C (NGC), a brain-specific transmembrane chondroitin sulfate proteoglycan. The major results obtained are as follows.
1. A single EGF-like module exists in the ectodomain of the NGC core protein. A recombinant peptide containing the EGF-like module promoted phosphorylation of EGF-receptors, ErbB2 and ErbB3, and proliferation of cell lines that express all of four EGF-receptors, indicating that NGC is a novel member of the EGF family.
2. A recombinant NGC ectodomain promoted neurite elongation from neocortical neurons in culture. Inhibitors of phosphatidylinositol 3-kinase and of protein kinase C prevented NGC-mediated neurite elongation. The active sites for promotion of neurite elongation existed on the acidic domain and the EGF-like domain of the NGC ectodomain.
3. NGC bore achondroitin sulfate (CS) side chain only at Ser-123 on the core protein. NGC isolated from postnatal day-10 rat brains had a relatively high content of E-disaccharide units, an oversulfated CS disaccharide unit, compared with neurocan and phosphacan.
4. CS-E, a commercial preparation of highly sulfated CS, promoted FGF-2-mediated proliferation of neural stem cells. To identify the minimum size of CS-E-derived oligosaccharides that have a promotive activity for neural stem cell growth, CS-E was partially degraded, and activities of the degradation products with different molecular sizes were determined. A fraction of 3 kDa (〜12 sugars) showed a strong activity for promotion of neural stem cell proliferation. Quartz-crystal microbalance method revealed that both the 3 kDa fraction and a hexasulfated hexasaccharide had a high affinity to FGF-2,but the latter did not have the promotive activity for cell proliferation.
Thus, the EGF-like domain of the NGC core protein and a 3 kDa oligosaccharide derived from E-unit-rich CS have properties that can be applicable to repair of brain injuries.
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